R-Napropamide Potentially Regulates Cadmium Accumulation in Arabidopsis Shoots through Transport Channel Modulation.

Heavy metal contamination in soils poses a significant environmental threat to human health. This study examines the effects of the chiral herbicide napropamide (NAP) on Arabidopsis thaliana, focusing on growth metrics and cadmium (Cd) accumulation. R-NAP does not adversely affect plant growth compared to the control, whereas S-NAP significantly reduces root length and fresh weight. Notably, R-NAP markedly increases Cd accumulation in the shoots, exceeding levels observed in the control and S-NAP. This increase coincides with reduced photosynthetic efficiency. Noninvasive electrode techniques reveal a higher net Cd absorption flux in the root mature zone under R-NAP than S-NAP, although similar to the control. Transcriptomic analysis highlights significant stereoisomer differences in Cd transporters, predominantly under R-NAP treatment. SEM and molecular docking simulations support that R-NAP primarily upregulates transporters such as HMA4. The results suggest careful management of herbicides like R-NAP in contaminated fields to avoid excessive heavy metal buildup in crops.

Integrated Bioinformatics Analysis Revealed Immune Checkpoint Genes Relevant to Type 2 Diabetes.

Objective: Chronic low-grade inflammation of the pancreatic islets is the characteristic of type 2 diabetes (T2D), and some of the immune checkpoints may play important roles in the pancreatic islet inflammation. Thus, we aim to explore the immune checkpoint genes (ICGs) associated with T2D, thereby revealing the role of ICGs in the pathogenesis of T2D based on bioinformatic analyses. Methods: Differentially expressed genes (DEGs) and immune checkpoint genes (ICGs) of islets between T2D and control group were screened from datasets of the Gene Expression Omnibus (GEO). A risk model was built based on the coefficients of ICGs calculated by ridge regression. Functional enrichment analysis and immune cell infiltration estimation were conducted. Correlations between ICGs and hub genes, T2D-related disease genes, insulin secretion genes, and beta cell function-related genes were analyzed. Finally, we conducted RT-PCR to verify the expression of these ICGs. Results: In total, pancreatic islets from 19 cases of T2D and 84 healthy subjects were included. We identified 458 DEGs. Six significantly upregulated ICGs (CD44, CD47, HAVCR2, SIRPA, TNFSF9, and VTCN1) in T2D were screened out. These ICGs were significantly correlated with several hub genes and T2D-related genes; furthermore, they were correlated with insulin secretion and ß cell function-related genes. The analysis of immune infiltration showed that the concentrations of eosinophils, T cells CD4 naive, and T cells regulatory (Tregs) were significantly higher, but CD4 memory resting T cells and monocytes were lower in islets of T2D patients. The infiltrated immune cells in T2D pancreatic islet were associated with these six ICGs. Finally, the expression levels of four ICGs were confirmed by RT-PCR, and three ICGs were validated in another independent dataset. Conclusion: In conclusion, the identified ICGs may play an important role in T2D. Identification of these differential genes may provide new clues for the diagnosis and treatment of T2D.

Limosilactobacillus fermentum TY-S11 ameliorates hypercholesterolemia via promoting cholesterol excretion and regulating gut microbiota in high-cholesterol diet-fed apolipoprotein E-deficient mice.

Hypercholesterolemia is a metabolic disease characterized by elevated cholesterol level in the blood, which is a risk factor for many diseases. Probiotic intervention may be one of the ways to improve hypercholesterolemia. In this study, three strains with better cholesterol removal ability were selected from 60 strains of lactic acid bacteria, and were orally administered to apolipoprotein E-deficient mice on a high-cholesterol diet. Among the three strains, only Limosilactobacillus fermentum TY-S11, which was isolated from the intestine of a longevity person, significantly improved serum and liver lipid levels in hypercholesterolemic mice. Further study found that L. fermentum TY-S11 promoted the excretion of cholesterol in the feces and inhibited the absorption of cholesterol in the small intestine. As for gut microbiota, the results showed that L. fermentum TY-S11 not only prevented the reduction of diversity caused by high-cholesterol diet, but also increased the contents of short-chain fatty acids in feces. These results confirmed the ameliorative effect of L. fermentum TY-S11 on hypercholesterolemia.

Precise mode control of laser-written waveguides for broadband, low-dispersion 3D integrated optics.

Three-dimensional (3D) glass chips are promising waveguide platforms for building hybrid 3D photonic circuits due to their 3D topological capabilities, large transparent windows, and low coupling dispersion. At present, the key challenge in scaling down a benchtop optical system to a glass chip is the lack of precise methods for controlling the mode field and optical coupling of 3D waveguide circuits. Here, we propose an overlap-controlled multi-scan (OCMS) method based on laser-direct lithography that allows customizing the refractive index profile of 3D waveguides with high spatial precision in a variety of glasses. On the basis of this method, we achieve variable mode-field distribution, robust and broadband coupling, and thereby demonstrate dispersionless LP21-mode conversion of supercontinuum pulses with the largest deviation of <0.1 dB in coupling ratios on 210 nm broadband. This approach provides a route to achieve ultra-broadband and low-dispersion coupling in 3D photonic circuits, with overwhelming advantages over conventional planar waveguide-optic platforms for on-chip transmission and manipulation of ultrashort laser pulses and broadband supercontinuum.

Foliar application of selenium and gibberellins reduce cadmium accumulation in soybean by regulating interplay among rhizosphere soil metabolites, bacteria community and cadmium speciation.

Both selenium (Se) and gibberellins (GA3) can alleviate cadmium (Cd) toxicity in plants. However, the application of Se and GA3 as foliar spray to against Cd stress on soybean and its related mechanisms have been poorly explored. Herein, this experiment evaluated the effects of Se and GA3 alone and combined application on soybean rhizosphere microenvironment, Cd accumulation and growth of soybean seedlings. The results revealed that both Se and GA3 can effectively decrease the accumulation of Cd in soybean seedlings. Foliar application of Se, GA3 and their combination reduced Cd contents in soybean seedlings respectively by 21.70 %, 27.53 % and 45.07 % when compared with the control treatment, suggest a synergistic effect of Se and GA3 in decreasing Cd accumulation. Se and GA3 also significantly increased diversity and abundance of the metabolites in rhizosphere, which consequently played an important role in shaping rhizosphere bacteria community and improve rhizosphere soil physicochemical properties of Cd contaminated soil, as well as decreased the Cd available forms contents but enhance the immobilized form levels. Overall, this study affords a novel approach on mitigating Cd accumulation in soybean seedlings which is attributed to Se and GA3 regulated interplay among rhizosphere soil metabolites, bacteria community and cadmium speciation.

OsRCI-1-Mediated GLVs Enhance Rice Resistance to Brown Planthoppers.

Green leaf volatiles (GLVs) play pivotal roles in plant anti-herbivore defense. This study investigated whether the rice 13-lipoxygense gene OsRCI-1 is involved in GLV production and plant defense in rice. The overexpression of OsRCI-1 (oeRCI lines) in rice resulted in increased wound-induced levels of two prominent GLVs, cis-3-hexen-1-ol and cis-3-hexenal. In a previous study, we found that the overexpression of OsRCI-1 reduced the colonization by the rice brown planthopper (BPH, Nilaparvata lugens) but increased the attractiveness to the egg parasitoid Anagrus nilaparvatae compared to wild-type (WT) plants. This study found that when cis-3-hexen-1-ol, but not cis-3-hexenal, was added to WT plants, it could change the BPH's colonization preference, i.e., more BPHs preferred to colonize the oeRCI lines. The exogenous application of cis-3-hexen-1-ol or cis-3-hexenal to BPH-infested WT plants could weaken or overturn the preference of A. nilaparvatae for oeRCI lines. However, field experiments revealed that only cis-3-hexenal was attractive to the parasitoid and increased the parasitism rates of BPH eggs. These results indicate that OsRCI-1 is involved in rice GLV production and therefore modulates both direct and indirect defense in rice.

Evidence of Surface-Tension Lowering of Atmospheric Aerosols by Organics from Field Observations in an Urban Atmosphere: Relation to Particle Size and Chemical Composition.

Surface-active organics lower the aerosol surface tension (σs/a), leading to enhanced cloud condensation nuclei (CCN) activity and potentially exerting impacts on the climate. Quantification of σs/a is mainly limited to laboratory or modeling work for particles with selected sizes and known chemical compositions. Inferred values from ambient aerosol populations are deficient. In this study, we propose a new method to derive σs/a by combining field measurements made at an urban site in northern China with the κ-Köhler theory. The results present new evidence that organics remarkably lower the surface tension of aerosols in a polluted atmosphere. Particles sized around 40 nm have an averaged σs/a of 53.8 mN m-1, while particles sized up to 100 nm show σs/a values approaching that of pure water. The dependence curve of σs/a with the organic mass resembles the behavior of dicarboxylic acids, suggesting their critical role in reducing the surface tension. The study further reveals that neglecting the σs/a lowering effect would result in lowered ultrafine CCN (diameter <100 nm) concentrations by 6.8-42.1% at a typical range of supersaturations in clouds, demonstrating the significant impact of surface tension on the CCN concentrations of urban aerosols.

Glycerol-driven adaptive evolution for the production of low-molecular-weight Welan gum: Characterization and activity evaluation.

Through adaptive laboratory evolution (ALE) of Sphingomonas sp. ATCC 31555, fermentation for production of low-molecular-weight welan gum (LMW-WG) was performed using glycerol as sole carbon source. During ALE, GPC-MALS analysis revealed a gradual decrease in WG molecular weight with the increase of adaptation cycles, accompanied by changes in solution conformation. LMW-WG was purified and structurally analyzed using GPC-MALS, monosaccharide composition analysis, infrared spectroscopy, NMR analysis, atomic force microscopy, and scanning electron microscopy. Subsequently, LMW-WG obtains hydration, transparency, antioxidant activity, and rheological properties. Finally, an in vitro simulation colon reactor was used to evaluate potential prebiotic properties of LMW-WG as dietary fiber. Compared with WG produced using sucrose as substrate, LMW-WG exhibited a fourfold reduction in molecular weight while maintaining moderate viscosity. Structurally, L-Rha nearly completely replaced L-Man. Furthermore, LMW-WG demonstrated excellent hydration, antioxidant activity, and high transparency. It also exhibited resistance to saliva and gastrointestinal digestion, showcasing a favorable colonization effect on Bifidobacterium, making it a promising symbiotic agent.

Phosphorus deficiency alleviates iron limitation in Synechocystis cyanobacteria through direct PhoB-mediated gene regulation.

Iron and phosphorus are essential nutrients that exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. Here, we show that phosphorus deficiency increases the growth of iron-limited cyanobacteria (Synechocystis sp. PCC 6803) through a PhoB-mediated regulatory network. We find that PhoB, in addition to its well-recognized role in controlling phosphate homeostasis, also regulates key metabolic processes crucial for iron-limited cyanobacteria, including ROS detoxification and iron uptake. Transcript abundances of PhoB-targeted genes are enriched in samples from phosphorus-depleted seawater, and a conserved PhoB-binding site is widely present in the promoters of the target genes, suggesting that the PhoB-mediated regulation may be highly conserved. Our findings provide molecular insights into the responses of cyanobacteria to simultaneous iron/phosphorus nutrient limitation.

3D Laser Writing of Low-Loss Cross-Section-Variable Type-I Optical Waveguide Passive/Active Integrated Devices in Single Crystals.

Optical waveguides fabricated in single crystals offer crucial passive/active optical components for photonic integrated circuits. Single crystals possess inherent advantages over their amorphous counterpart, such as lower optical losses in visible-to-mid-infrared band, larger peak emission cross-section, higher doping concentration. However, the writing of Type-I positive refractive index modified waveguides in single crystals using femtosecond laser technology presents significant challenges. Herein, this work introduces a novel femtosecond laser direct writing technique that combines slit-shaping with an immersion oil objective to fabricate low-loss Type-I waveguides in single crystals. This approach allows for precise control of waveguide shape, size, mode-field, and refractive index distribution, with a spatial resolution as high as 700 nm and a high positive refractive index variation on the order of 10-2, introducing new degrees of freedom to design and fabricate passive/active optical waveguide devices. As a proof-of-concept, this work successfully produces a 7 mm-long circular-shaped gain waveguide (≈10 µm in diameter) in an Er3+-doped YAG single crystal, exhibiting a propagation loss as low as 0.23 dB cm-1, a net gain of ≈3 dB and a polarization-insensitive character. The newly-developed technique is theoretically applicable to arbitrary single crystals, holding promising potential for various applications in integrated optics, optical communication, and photonic quantum circuits.

ABA-importing transporter (AIT1) synergies enhances exogenous ABA minimize heavy metals accumulations in Arabidopsis.

Exogenous abscisic acid (ABA) presents a novel approach to mitigate heavy metal (HM) accumulation in plants, yet its efficacy against multiple HMs and potential enhancement methods remain underexplored. In this study, we demonstrated that the exogenous ABA application simultaneously decreased Zn, Cd and Ni accumulation by 22-25 %, 27-39 % and 60-62 %, respectively, in wild-type (WT) Arabidopsis. Conversely, ABA reduced Pb in shoots but increased its root concentration. ABA application also modulated the expression of HM uptake genes, inhibiting IRT1, NRAMP1, NRAMP4, and HMA3, and increasing ZIP1 and ZIP4 expressions. Further analysis revealed that overexpressing the ABA-importing transporter (AIT1) in plants intensified the reduction of Cd, Zn, and Ni, compared to WT. However, the inhibitory effect of exogenous ABA on Pb accumulation was mitigated in shoots with higher AIT1 expression. Furthermore, HMs-induced growth inhibition and the damage to photosynthesis were also alleviated with ABA treatment. Conclusively, AIT1's synergistic effect with ABA effectively reduces Cd, Zn and Ni accumulation, offering a synergistic approach to mitigate HM stress in plants.

Self-Control, Openness, Personal Need for Structure and Compensatory Control Change: A Serial Mediation Investigation.

In the aftermath of the COVID-19 pandemic, numerous studies have indicated that individuals are confronting a diminished sense of control. Compensatory control theory suggests that individuals strive to mitigate this loss by modifying their behavior. The present study aims to investigate the relationship between self-control and compensatory control change during the COVID-19 pandemic, as well as the mediating effects of openness and the personal need for structure. Participants completed an online questionnaire consisting of Personal Need for Structure Scale, Self-Control Scale, Openness Scale and Compensatory Control Change Scale. The results showed that the compensatory control change increased after the outbreak. Moreover, a serial mediation was found: openness and the personal need for structure partially mediated the relationship between self-control and compensatory control change. The results indicate that the COVID-19 pandemic has led to an increase in compensatory control behaviors, especially among those with pronounced self-control. High self-control individuals are found to exhibit greater openness, reducing their personal need for structure, in effect enhancing their compensatory control change. These findings highlight the critical role of self-control in sustaining a sense of control, which is vital for understanding psychological health management in the context of public health events.

Isolation of a facultative methanotroph Methylocystis iwaonis SD4 from rice rhizosphere and establishment of rapid genetic tools for it.

Methanotrophs of the genus Methylocystis are frequently found in rice paddies. Although more than ten facultative methanotrophs have been reported since 2005, none of these strains was isolated from paddy soil. Here, a facultative methane-oxidizing bacterium, Methylocystis iwaonis SD4, was isolated and characterized from rhizosphere samples of rice plants in Nanjing, China. This strain grew well on methane or methanol but was able to grow slowly using acetate or ethanol. Moreover, strain SD4 showed sustained growth at low concentrations of methane (100 and 500 ppmv). M. iwaonis SD4 could utilize diverse nitrogen sources, including nitrate, urea, ammonium as well as dinitrogen. Strain SD4 possessed genes encoding both the particulate methane monooxygenase and the soluble methane monooxygenase. Simple and rapid genetic manipulation methods were established for this strain, enabling vector transformation and unmarked genetic manipulation. Fast growth rate and efficient genetic tools make M. iwaonis SD4 an ideal model to study facultative methanotrophs, and the ability to grow on low concentration of methane implies its potential in methane removal.

Portable and Flexible Hydrogel Sensor for On-Site Atrazine Assay on Agricultural Products.

There is growing attention focused toward the problems of ecological sustainability and food safety raised from the abuse of herbicides, which underscores the need for the development of a portable and reliable sensor for simple, rapid, and user-friendly on-site analysis of herbicide residues. Herein, a novel multifunctional hydrogel composite is explored to serve as a portable and flexible sensor for the facile and efficient analysis of atrazine (ATZ) residues. The hydrogel electrode is fabricated by doping graphite-phase carbon nitride (g-C3N4) into the aramid nanofiber reinforced poly(vinyl alcohol) hydrogel via a simple solution-casting procedure. Benefiting from the excellent electroactivity and large specific surface area of the solid nanoscale component, the prepared hydrogel sensor is capable of simple, rapid, and sensitive detection of ATZ with a detection limit down to 0.002 ng/mL and per test time less than 1 min. After combination with a smartphone-controlled portable electrochemical analyzer, the flexible sensor exhibited satisfactory analytical performance for the ATZ assay. We further demonstrated the applications of the sensor in the evaluation of the ATZ residues in real water and soil samples as well as the user-friendly on-site point-of-need detection of ATZ residues on various agricultural products. We envision that this flexible and portable sensor will open a new avenue on the development of next-generation analytical tools for herbicide monitoring in the environment and agricultural products.

Associations between serum 25-hydroxyvitamin D and prognosis of chronic kidney disease: a prospective cohort study.

BACKGROUND AND OBJECTIVES: 25-hydroxyvitamin D [25(OH)D] deficiency is prevalent in patients with chronic kidney disease (CKD), the associations between serum 25(OH)D levels and mortality in patients with CKD remain unclear, and this study aimed to explore these associations further. METHODS: 4989 participants with CKD were enrolled in the study, and the Cox regression model was used to assess the effects of serum 25(OH)D concentrations on mortality risk. A restricted cubic spline model was used to explore the dose-response relationships, and threshold effect analysis was performed based on inflection points identified by a two-piecewise linear regression model. In addition, subgroup and sensitivity analyses were employed. RESULTS: 1255 participants died during a mean follow-up period of 70 months. Compared with the 25(OH)D-deficient group, the fully adjusted hazard ratios and 95% confidence intervals for the 25(OH)D-adequate group were 0.631 (0.545, 0.730) for all-cause mortality, 0.569 (0.435, 0.743) for cardiovascular mortality, 0.637 (0.461, 0.878) for hypertension mortality, and cancer mortality was 0.596 (0.426, 0.834). The inflection points of serum 25(OH)D concentration affecting all-cause and cardiovascular mortality were 89 nmol/L, and 107 nmol/L, respectively. Subgroup analyses and interaction tests suggested that the effects varied across populations. The results of sensitivity analyses indicated a reliable correlation. CONCLUSION: We found an association between serum 25(OH)D concentrations and the prognosis of patients with CKD as a reliable predictor of early intervention and intensive care.

Graphitic carbon nitride alleviates cadmium toxicity to soybeans through nitrogen supply.

Graphitic carbon nitride (g-C3N4) is a promising candidate for heavy metal remediation, primarily composed of carbon (C) and nitrogen (N). It has been demonstrated that g-C3N4 adjusts rhizosphere physicochemical conditions, especially N conditions, alleviating the absorption and accumulation of Cadmium (Cd) by soybeans. However, the mechanisms by which g-C3N4 induces N alterations to mitigates plant uptake of Cd remain unclear. This study investigated the impact of g-C3N4-mediated changes in N conditions on the accumulation of Cd by soybeans using pot experiments. It also explored the microbiological mechanisms underlying alterations in soybean rhizospheric N cycling induced by g-C3N4. It was found that g-C3N4 significantly increased N content in the soybean rhizosphere (p < 0.05), particularly in terms of available nitrogen (AN) of nitrate and ammonium. Plants absorbed more ammonium nitrogen (NH4⁺-N), the content of which in the roots showed a significant negative correlation with Cd concentration in plant (p < 0.05). Additionally, g-C3N4 significantly affected rhizospheric functional genes associated with N cycling (p < 0.05) by increasing the ratio of the N-fixation functional gene nifH and decreasing the ratios of functional genes amoA and nxrA involved in nitrification. This enhances soybean's N-fixing potential and suppresses denitrification potential in the rhizosphere, preserving NH4⁺-N. Niastella, Flavisolibacter, Opitutus and Pirellula may play a crucial role in the N fixation and preservation process. In summary, the utilization of g-C3N4 offers a novel approach to ensure safe crop production in Cd-contaminated soils. The results of this study provide valuable data and a theoretical foundation for the remediation of Cd polluted soils.

Integrated transcriptomic, metabolomic, and functional analyses unravel the mechanism of bagging delaying fruit cracking of pomegranate (Punica granatum L.).

The economic impact of fruit cracking in pomegranate products is substantial. In this study, we present the inaugural comprehensive analysis of transcriptome and metabolome in the outermost pericarp of pomegranate fruit in bagging conditions. Our investigation revealed a notable upregulation of differentially expressed genes (DEGs) associated with the calcium signaling pathway (76.92%) and xyloglucan endotransglucosylase/hydrolase (XTH) genes (87.50%) in the fruit peel of non-cracking fruit under bagging. Metabolomic analysis revealed that multiple phenolics, flavonoids, and tannins were identified in pomegranate. Among these, calmodulin-like 23 (PgCML23) exhibited a significant correlation with triterpenoids and demonstrated a marked upregulation under bagging treatment. The transgenic tomatoes overexpressing PgCML23 exhibited significantly higher cellulose content and xyloglucan endotransglucosylase (XET) enzyme activity in the pericarp at the red ripening stage compared to the wild type. Conversely, water-soluble pectin content, polygalacturonase (PG), and ß-galactosidase (ß-GAL) enzyme activities were significantly lower in the transgenic tomatoes. Importantly, the heterologous expression of PgCML23 led to a substantial reduction in the fruit cracking rate in tomatoes. Our findings highlight the reduction of fruit cracking in bagging conditions through the manipulation of PgCML23 expression.

ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway.

Breast cancer has the highest global incidence and mortality rates among all cancer types. Abnormal expression of the Annexin family has been observed in different malignant tumors, including upregulated ANXA9 in breast cancer. We found highly expressed ANXA9 in metastatic breast cancer tissues, which is correlated with breast cancer progression. In vitro, the functional experiments indicated ANXA9 influenced breast cancer proliferation, motility, invasion, and apoptosis; in vivo, downregulation of ANXA9 suppressed breast cancer xenograft tumor growth and lung metastasis. Mechanically, on one side, we found that ANXA9 could mediate S100A4 and therefore regulate AKT/mTOR/STAT3 pathway to participate p53/Bcl-2 apoptosis; on the other side, we found ANXA9 transferred S100A4 from cells into the tumor microenvironment and mediated the excretion of cytokines IL-6, IL-8, CCL2, and CCL5 to participate angiogenesis via self- phosphorylation at site Ser2 and site Thr69. Our findings demonstrate significant involvement of ANXA9 in promoting breast cancer progression, thereby suggesting that therapeutic intervention via targeting ANXA9 may be effective in treating metastatic breast cancer.

Construction of Magnesium Phosphate Chemical Conversion Coatings with Different Microstructures on Titanium to Enhance Osteogenesis and Angiogenesis.

Titanium (Ti) and its alloys are widely used as hard tissue substitutes in dentistry and orthopedics, but their low bioactivity leads to undesirable osseointegration defects in the early osteogenic phase. Surface modification is an important approach to overcome these problems. In the present study, novel magnesium phosphate (MgP) coatings with controllable structures were fabricated on the surface of Ti using the phosphate chemical conversion (PCC) method. The effects of the microstructure on the physicochemical and biological properties of the coatings on Ti were researched. The results indicated that accelerators in PCC solution were important factors affecting the microstructure and properties of the MgP coatings. In addition, the coated Ti exhibited excellent hydrophilicity, high bonding strength, and good corrosion resistance. Moreover, the biological results showed that the MgP coatings could improve the spread, proliferation, and osteogenic differentiation of mouse osteoblast cells (MC3T3-E1) and vascular differentiation of human umbilical vein endothelial cells (HUVECs), indicating that the coated Ti samples had a great effect on promoting osteogenesis and angiogenesis. Overall, this study provided a new research idea for the surface modification of conventional Ti to enhance osteogenesis and angiogenesis in different bone types for potential biomedical applications.

Design, Synthesis, and Biological Evaluation of Novel Cinnamide Derivatives as Neuroprotective Agents for the Treatment of Cerebral Ischemia.

BACKGROUND: Ischemic stroke, the most common type of cerebrovascular accident, is a major cause of severe disability among adults worldwide. Although there has been progress in interventions for ischemic stroke in the past decades, there is no effective treatment to prevent brain damage in acute ischemic stroke. Therefore, it is urgent to develop novel neuroprotective agents with a wide therapeutic time window to provide a better prognosis for ischemic stroke patients. OBJECTIVE: The current study aimed to synthesize novel derivatives with substituent cinnamide scaffolds, evaluate biological activity, and obtain neuroprotective agents. METHODS: The target compounds were synthesized using classical methods of medicinal chemistry. The neuroprotective effects in vitro against Glu-induced neurotoxicity injury were evaluated in PC12 cells by MTT assay. The cell apoptosis was analyzed by flow cytometer. The proteins were detected by western blotting. The neuroprotective activities in vivo were determined in two in vivo models of global and focal cerebral ischemia. RESULTS: Among the title compounds, 9t, 9u, 9y, and 9z exhibited good neuroprotection in vivo and in vitro, which were selected and further studied to determine their mechanism of action. 9t, 9u, 9y and 9z protected PC12 cells against glutamate-induced apoptosis in a dose-dependent manner via caspase-3 pathway. Moreover, the four compounds significantly reduced brain infarct area and exhibited excellent neuroprotective activities in the in vivo MCAO model. CONCLUSION: Compounds 9t, 9u, 9y, and 9z, as potent neuroprotective agents with anti- neurotoxicity activity in vitro and anticerebral infarction efficacy in vivo, might serve as a useful molecular tool for further physiology and pathophysiology function studies, leading to potential clinical therapeutic agents for ischemic injury.